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Dissertation zugänglich unter
URN: urn:nbn:de:gbv:18-36452
URL: http://ediss.sub.uni-hamburg.de/volltexte/2008/3645/


Neural recognition molecule CHL1 : regulation of the activity of the trimeric protein complex Csp/Hsc70/Sgt and synaptic vesicle recycling in Mus musculus (Linnaeus, 1758)

Das neurale Zellerkennungsmolekül CHL1 : Regulation der Aktivität des trimeren Proteinkomplexes Csp/Hsc70/Sgt und des synaptischen Vesikelrecyclings in Mus musculus (Linnaeus, 1758)

Andreyeva, Aksana

Originalveröffentlichung: (2008) Leshchyns'ka, I., Sytnyk, V., Richter, M., Andreyeva, A., Puchkov, D., Schachner, M. (2006). The adhesion molecule CHL1 regulates uncoating of clathrin-coated synaptic vesicles. Neuron. 52 (6), 1011-1025.
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Freie Schlagwörter (Englisch): CHL1 , Hsc70 , Csp , Sgt , SNARE
Basisklassifikation: 42.13 , 42.15
Institut: Biologie
DDC-Sachgruppe: Biowissenschaften, Biologie
Dokumentart: Dissertation
Hauptberichter: Schachner, Melitta (Prof. Dr.)
Sprache: Englisch
Tag der mündlichen Prüfung: 28.03.2008
Erstellungsjahr: 2008
Publikationsdatum: 21.04.2008
Kurzfassung auf Englisch: In this study the regulation of chaperone activity by the cell recognition molecule CHL1 (close homologue of L1) is analyzed. Previously it was shown that CHL1 is able to interact via its intracellular domain with the chaperone Hsc70 (70 kDa heat shock cognate protein), which is constitutively expressed in the cell. Here we demonstrate that CHL1 via its intracellular domain modulates the chaperone function in synapses. CHL1 regulates the refolding activity of synaptic chaperons Hsc70, Csp (cysteine string protein) and alphaSgt (small glutamine-rich tetratricopeptide repeat-containing protein) via the direct interactions with these proteins. In vitro protein binding assay and the analysis of the complexes that are present on synaptic vesicles and synaptic plasma membranes show the predominant formation of CHL1/Hsc70/alphaSgt and CHL1/Csp complexes. We found that the substrate for CHL1/Hsc70/alphaSgt chaperone complex is Snap25 (synaptosomal associated protein of 25 kDa), whereas CHL1/Csp complex refolds Vamp2 (vesicle-associated membrane protein). Snap25, Vamp2 together with Syntaxin1 assemble the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex that participates in the fusion of synaptic vesicles with the presynaptic plasma membrane during exocytosis. In CHL1 deficient synaptosomes we observed reduced ability of the components of the SNARE machinery to re-associate. On the other hand, stressful conditions, such as exposure to heat or prolonged synaptic activity, result in a pronounced degradation of SNARE complex components in the brain of CHL1 deficient mice. The defect of SNARE machinery formation following the prolonged stimulation of synaptic activity leads to the inhibition of the synaptic vesicle recycling in CHL1 deficient neurons. In other words, CHL1 deficient neurons are not able to sustain prolonged synaptic activity. We also show that CHL1 is involved in synaptic vesicle recycling by the modulation of clathrin-uncoating function of Hsc70. The obtained data suggest that cell recognition molecule CHL1 participates in two steps of synaptic vesicle recycling: in exocytosis as a modulator of chaperons that refold SNARE proteins and in endocytosis by the regulation of uncoating of clathrin-coated synaptic vesicles.

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